Background SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation–perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efficacy of oral sildenafil in treating COVID-19 inpatients showing perfusion abnormalities in sCTA. Methods Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafil (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were differences in oxygenation parameters measured daily during follow-up (PaO 2 /FiO 2 ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis. Results Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41–68] years. No significant differences in mean PaO 2 /FiO 2 ratios and A-a gradients were found between groups (repeated-measures ANOVA p = 0.67 and p = 0.69). IMV was required in 4 patients who received placebo and none in the sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly shorter median length of hospital stay than the placebo group (9 IQR 7–12 days vs. 12 IQR 9–21 days, p = 0.04). Conclusions No statistically significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results. Trial Registration : Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 . Supplementary Information The online version contains supplementary material available at 10.1186/s13054-021-03885-y.
【저자키워드】 COVID-19, mechanical ventilation, intensive care unit, Length of stay, Sildenafil, blood gas analysis, Subtraction CT angiography, Ventilation–perfusion ratio, 【초록키워드】 Treatment, SARS-CoV-2, Efficacy, Hospitalized, hospital, randomized trial, Infection, lung, outcome, ICU, Computed tomography, Registration, Randomized, placebo-controlled trial, therapeutic, Patient, non-invasive ventilation, Placebo, Follow-up, group, mortality rates, Admission, parameters, Invasive mechanical ventilation, COVID-19 patient, lung parenchyma, Oxygenation, Hospital stay, ventilatory support, Inpatient, Regulation, significant difference, control group, intervention group, supplementary material, median age, statistically significant difference, participant, treating COVID-19, abnormality, parameter, Affect, IMV, secondary, intention-to-treat basis, hypoperfusion, Seven, Result, enrolled, performed, evaluate, required, conducted, was performed, median, characterized, 1:1, eligible adult, IQR, PaO, patients with COVID-19, repeated-measures ANOVA, significantly shorter, the placebo group, were excluded, 【제목키워드】 randomized trial, patients with COVID-19,